Inform women who ask that estrogen alone has not been shown to increase the risk of breast cancer.

PHILADELPHIA, April 9 - One woman in four who tries to stop hormone replacement therapy has severe rebound symptoms and most resume HRT, according to an investigator with the Women's Health Initiative (WHI).

A prescription for estrogen to ease hot flashes and night sweats may "be starting women on the path to chronic hormone replacement," warned Marcia L. Stefanick, Ph.D., a professor of medicine at Stanford and an investigator with the WHI, at the American College of Physicians meeting here.

Dr. Stefanick said that some follow-up analyses conducted by WHI researchers suggest that "about 26% cannot stop the hormone."

Her advice to clinicians was to weigh the undeniable benefit of estrogen for treatment of vasomotor symptoms -- "it's the best game in town" -- against the risk "that you may be setting a woman up for chronic reliance on hormone therapy."

Moreover, she said that many of the women who are unable to kick the hormone habit actually had mild symptoms before starting HRT. "It is almost as if the hormone exposure somehow sets the woman up for worse symptoms," she said.

If women do have severe rebound symptoms, she advised putting them back on hormones but at a lower dose. "After the woman is stabilized, try tapering the dose by going to an every other day dosing or by skipping weekends," she said.

Dr. Stefanick's lecture, "Treatment of Menopausal Symptoms in the Post-WHI Era," was part of the ongoing effort by the National Institutes of Health to clarify the take home messages from the massive hormone therapy trial that it stopped almost four years ago.

Many women and a significant number of physicians still don't understand that WHI was actually designed as two trials, she said. And the results of those two trials are not identical.

For example, Dr. Stefanick said, the often over-shadowed estrogen-only trial has now provided clear evidence "that estrogen alone does not increase the risk of breast cancer, and women need to know that."

The WHI, which was designed to test hormones against a wide range of endpoints ranging from cardiovascular disease and osteoporosis to cognition and cancer, included two distinct placebo-controlled arms. One tested Prempro, an estrogen-progestin combination, and the other tested Premarin, an unopposed conjugated equine estrogen.

The Prempro arm recruited more than 16,600 women, ages 50 to 79, and randomized 8,506 of them to Prempro at 2.5 mg daily and the rest (8,102) to placebo. In July 2002 the National Institutes of Health announced that it was stopping the study because the combination was associated with an increase in the relative risk of heart attack, stroke, and venous thrombosis as well as an increase in the risk of breast cancer.

But the other part of the WHI was the estrogen-only study, Dr. Stefanick said. "That was a study of women who had their uteri surgically removed," and in that study there was also a significant increase in the risk of stroke, but the findings on cardiovascular disease and DVT were neutral.

That study enrolled 10,739 women ages 50 to 79 and assigned them to either Premarin (conjugated equine estrogen at 0.625) or placebo.

An unexpected finding was that "women randomized to estrogen had a 23% reduction in the relative risk of breast cancer. Although this was statistically significant, it was quite different form the increased risk observed in the estrogen-plus-progestin trial, she said. "So the new message to women is that if you only go on estrogen, we don't have evidence that this is going to increase your risk of breast cancer and we think it probably doesn't."

But because a significant number of women "will have difficulty coming off the hormone," Dr. Stefanick cautioned clinicians to be "very careful before you start down that path."

And when hormones are initiated "we recommend lower doses and for shorter times." Asked to define "shorter time," she said the recommendations are for two to three years and she advised trying to "come off hormones after a year."

Finally, she said that while some women will have symptoms for several years "research suggests that the worst symptoms last only about a year in most women. I think that should be explained to women who are considering hormone therapy."

But for women who are extremely symptomatic, "estrogen works."

And women who are at low risk for heart attacks or stroke before taking hormones are "not going to high risk because you give them hormones. But for high risk women, the hormones could tip the scale."

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.